Development of T cell receptor repertoires during childhood in health and disease

By Emma A., Bunia A., Othilia FS., Tobias C. & Joanna R.

Group 21

Introduction

Based on the article Mitchell et al. (2022)
Allele repertoire development during childhood and type 1 diabetes
Two groups of patients, case and control
Returns four times for observations

Materials:

1. Data from immunoSEQ ANALYZER

Methods:

1. Base R
1. Tidyverse R
2. PCA analysis
3. MCA analysis

Data Description

Original data (01_dat_load.tsv)

[1] 359  12

# A tibble: 359 × 2
   sample_name sample_tags                                                      
   <chr>       <chr>                                                            
 1 310183_TCRB 06 Years, 6 Years at visit, Caucasian, Control, Control 022, GAD…
 2 310110_TCRB 0 Years at visit, 09 Months, 6.37808219178082 Years at diagnosis…
 3 310206_TCRB 0 Years at visit, 10 Months, 10.558904109589 Years at diagnosis,…
 4 310288_TCRB 09 Years, 9 Years at visit, 9.56986301369863 Years at diagnosis,…
 5 310271_TCRB 02 Years, 2 Years at visit, 6.87397260273973 Years at diagnosis,…
 6 310244_TCRB 05 Years, 18.0438356164384 Years at diagnosis, 5 Years at visit,…
 7 310137_TCRB 07 Years, 7 Years at visit, Caucasian, Control, Control 014, Fem…
 8 310258_TCRB 12 Years, 12 Years at visit, 12.958904109589 Years at diagnosis,…
 9 310127_TCRB 04 Years, 11.6821917808219 Years at diagnosis, 4 Years at visit,…
10 310300_TCRB 17 Years, 17 Years at visit, 17.7561643835616 Years at diagnosis…
# ℹ 349 more rows

[1] 10

Data Wrangling

Augmented data (03_dat_aug.tsv)

[1] 13824    24

# A tibble: 10 × 8
   sample_name case_control    id age_diagnosis antibody expression allele  
   <chr>       <chr>        <dbl>         <dbl> <chr>         <dbl> <chr>   
 1 310102_TCRB Case             1          13.0 GAD65             0 HLA_A   
 2 310102_TCRB Case             1          13.0 GAD65             0 HLA_A   
 3 310102_TCRB Case             1          13.0 GAD65             0 HLA_B   
 4 310102_TCRB Case             1          13.0 GAD65             0 HLA_B   
 5 310102_TCRB Case             1          13.0 GAD65             0 HLA_C   
 6 310102_TCRB Case             1          13.0 GAD65             0 HLA_C   
 7 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPA1
 8 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPA1
 9 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPB1
10 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPB1
# ℹ 1 more variable: subtype <chr>

Antibody Expression

Antibody Expression, PCA

HLA Expression

HLA Expression, MCA

Discussion

Patterns between antibody expressions. Suggests need for PCA.
Two components explain majority of variance in data.
Two clusters form between variables.
Dominant allele subtypes in case subjects.
Insufficient 2D variance explanation.

Limitations

Missing values for control subjects
Relatively small data set

Conclusion

Clear differences exist between case and control subjects, both in terms of antibody expression and in terms of allele subtypes.
Suggests that both antibody expression and allele subtype are involved in the development of diabetes in children.
Based on our results, HLA-DQB1*0202, HLA-B*4402, HLA-A*2402, and HLA-B*0702 show greater association with case than control. Further research would be required to determine their direct effect on type 1 diabetes.
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